JP2016539658A - テンポリンSHaのアナログおよびその使用 - Google Patents
テンポリンSHaのアナログおよびその使用 Download PDFInfo
- Publication number
- JP2016539658A JP2016539658A JP2016544764A JP2016544764A JP2016539658A JP 2016539658 A JP2016539658 A JP 2016539658A JP 2016544764 A JP2016544764 A JP 2016544764A JP 2016544764 A JP2016544764 A JP 2016544764A JP 2016539658 A JP2016539658 A JP 2016539658A
- Authority
- JP
- Japan
- Prior art keywords
- peptide
- group
- leishmania
- seq
- temporin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 108010053343 temporin Proteins 0.000 title description 60
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 187
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 53
- 230000009261 transgenic effect Effects 0.000 claims abstract description 15
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 11
- 239000002917 insecticide Substances 0.000 claims abstract description 6
- 239000003755 preservative agent Substances 0.000 claims abstract description 6
- 239000000417 fungicide Substances 0.000 claims abstract description 5
- 241000222722 Leishmania <genus> Species 0.000 claims description 60
- 150000001413 amino acids Chemical class 0.000 claims description 56
- 108020004707 nucleic acids Proteins 0.000 claims description 41
- 102000039446 nucleic acids Human genes 0.000 claims description 41
- 150000007523 nucleic acids Chemical class 0.000 claims description 41
- 208000015181 infectious disease Diseases 0.000 claims description 37
- 241000894006 Bacteria Species 0.000 claims description 36
- 230000000845 anti-microbial effect Effects 0.000 claims description 30
- 244000045947 parasite Species 0.000 claims description 30
- 239000013598 vector Substances 0.000 claims description 28
- 230000014509 gene expression Effects 0.000 claims description 26
- 229910052700 potassium Inorganic materials 0.000 claims description 26
- 230000000813 microbial effect Effects 0.000 claims description 21
- 239000013604 expression vector Substances 0.000 claims description 15
- 239000003814 drug Substances 0.000 claims description 14
- 150000003839 salts Chemical class 0.000 claims description 10
- 241000233866 Fungi Species 0.000 claims description 9
- 239000000126 substance Substances 0.000 claims description 9
- 241000700605 Viruses Species 0.000 claims description 8
- 239000007943 implant Substances 0.000 claims description 8
- 229910052721 tungsten Inorganic materials 0.000 claims description 8
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
- 229910052720 vanadium Inorganic materials 0.000 claims description 7
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 230000002335 preservative effect Effects 0.000 claims description 2
- 230000000855 fungicidal effect Effects 0.000 claims 1
- 108700042778 Antimicrobial Peptides Proteins 0.000 abstract description 29
- 102000044503 Antimicrobial Peptides Human genes 0.000 abstract description 29
- 239000004599 antimicrobial Substances 0.000 abstract description 5
- 210000004027 cell Anatomy 0.000 description 67
- 235000001014 amino acid Nutrition 0.000 description 47
- 229940024606 amino acid Drugs 0.000 description 47
- 241000196324 Embryophyta Species 0.000 description 37
- 230000000694 effects Effects 0.000 description 28
- 238000000034 method Methods 0.000 description 23
- 238000012360 testing method Methods 0.000 description 18
- 108090000623 proteins and genes Proteins 0.000 description 17
- 239000002609 medium Substances 0.000 description 16
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 14
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 14
- 241000223104 Trypanosoma Species 0.000 description 14
- 230000012010 growth Effects 0.000 description 14
- 210000003743 erythrocyte Anatomy 0.000 description 13
- 239000000243 solution Substances 0.000 description 11
- 230000001580 bacterial effect Effects 0.000 description 9
- 230000002949 hemolytic effect Effects 0.000 description 9
- 239000013642 negative control Substances 0.000 description 9
- 241000269350 Anura Species 0.000 description 8
- 210000004899 c-terminal region Anatomy 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 8
- 210000002540 macrophage Anatomy 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- 239000003910 polypeptide antibiotic agent Substances 0.000 description 8
- 230000035755 proliferation Effects 0.000 description 8
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 7
- 231100000135 cytotoxicity Toxicity 0.000 description 7
- 230000003013 cytotoxicity Effects 0.000 description 7
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 7
- 239000002243 precursor Substances 0.000 description 7
- -1 tracycline Chemical compound 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 241000238631 Hexapoda Species 0.000 description 6
- 230000003698 anagen phase Effects 0.000 description 6
- 239000003242 anti bacterial agent Substances 0.000 description 6
- 230000003115 biocidal effect Effects 0.000 description 6
- 231100000263 cytotoxicity test Toxicity 0.000 description 6
- 210000002950 fibroblast Anatomy 0.000 description 6
- 230000002209 hydrophobic effect Effects 0.000 description 6
- 210000001616 monocyte Anatomy 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- 238000006467 substitution reaction Methods 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 208000004554 Leishmaniasis Diseases 0.000 description 5
- 108060001084 Luciferase Proteins 0.000 description 5
- 229930182555 Penicillin Natural products 0.000 description 5
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 5
- 230000000843 anti-fungal effect Effects 0.000 description 5
- 230000001461 cytolytic effect Effects 0.000 description 5
- 238000012217 deletion Methods 0.000 description 5
- 230000037430 deletion Effects 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 238000011534 incubation Methods 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 229940049954 penicillin Drugs 0.000 description 5
- 230000009466 transformation Effects 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 241000222120 Candida <Saccharomycetales> Species 0.000 description 4
- 241000222122 Candida albicans Species 0.000 description 4
- 108020004414 DNA Proteins 0.000 description 4
- 206010018910 Haemolysis Diseases 0.000 description 4
- 239000005089 Luciferase Substances 0.000 description 4
- 108010076504 Protein Sorting Signals Proteins 0.000 description 4
- 239000012980 RPMI-1640 medium Substances 0.000 description 4
- 241000269435 Rana <genus> Species 0.000 description 4
- 230000009471 action Effects 0.000 description 4
- 230000000844 anti-bacterial effect Effects 0.000 description 4
- 230000002141 anti-parasite Effects 0.000 description 4
- 229940088710 antibiotic agent Drugs 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 229910002091 carbon monoxide Inorganic materials 0.000 description 4
- 239000012091 fetal bovine serum Substances 0.000 description 4
- 235000013305 food Nutrition 0.000 description 4
- 230000008588 hemolysis Effects 0.000 description 4
- 230000001965 increasing effect Effects 0.000 description 4
- 244000052769 pathogen Species 0.000 description 4
- 239000013641 positive control Substances 0.000 description 4
- 230000003389 potentiating effect Effects 0.000 description 4
- 125000006239 protecting group Chemical group 0.000 description 4
- 235000018102 proteins Nutrition 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 4
- 229960005322 streptomycin Drugs 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- 230000000699 topical effect Effects 0.000 description 4
- 230000001988 toxicity Effects 0.000 description 4
- 231100000419 toxicity Toxicity 0.000 description 4
- 238000013518 transcription Methods 0.000 description 4
- 230000035897 transcription Effects 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 241000589158 Agrobacterium Species 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- 201000003883 Cystic fibrosis Diseases 0.000 description 3
- 241000194032 Enterococcus faecalis Species 0.000 description 3
- 241000588724 Escherichia coli Species 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 3
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 3
- 241000186781 Listeria Species 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 241001219289 Pelophylax saharicus Species 0.000 description 3
- 108091005804 Peptidases Proteins 0.000 description 3
- 241001336823 Rana ornativentris Species 0.000 description 3
- 241000191967 Staphylococcus aureus Species 0.000 description 3
- 206010047505 Visceral leishmaniasis Diseases 0.000 description 3
- 238000002835 absorbance Methods 0.000 description 3
- 125000000539 amino acid group Chemical group 0.000 description 3
- 230000032770 biofilm formation Effects 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 201000003146 cystitis Diseases 0.000 description 3
- 230000001472 cytotoxic effect Effects 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 230000004069 differentiation Effects 0.000 description 3
- 206010014665 endocarditis Diseases 0.000 description 3
- 230000002538 fungal effect Effects 0.000 description 3
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 3
- 230000009036 growth inhibition Effects 0.000 description 3
- 239000002054 inoculum Substances 0.000 description 3
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 3
- 229960000310 isoleucine Drugs 0.000 description 3
- 210000000265 leukocyte Anatomy 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 230000002503 metabolic effect Effects 0.000 description 3
- 244000005700 microbiome Species 0.000 description 3
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 3
- 201000001245 periodontitis Diseases 0.000 description 3
- 230000007505 plaque formation Effects 0.000 description 3
- 230000004481 post-translational protein modification Effects 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 239000007790 solid phase Substances 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- 235000000346 sugar Nutrition 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 2
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 2
- 241000588626 Acinetobacter baumannii Species 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 2
- 241000589155 Agrobacterium tumefaciens Species 0.000 description 2
- HJCMDXDYPOUFDY-WHFBIAKZSA-N Ala-Gln Chemical compound C[C@H](N)C(=O)N[C@H](C(O)=O)CCC(N)=O HJCMDXDYPOUFDY-WHFBIAKZSA-N 0.000 description 2
- 239000004475 Arginine Substances 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 2
- 208000035143 Bacterial infection Diseases 0.000 description 2
- 241000222173 Candida parapsilosis Species 0.000 description 2
- 108091026890 Coding region Proteins 0.000 description 2
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 2
- 206010011409 Cross infection Diseases 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 2
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 2
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 2
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 2
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 2
- 241000222695 Leishmania panamensis Species 0.000 description 2
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 2
- 206010024305 Leukaemia monocytic Diseases 0.000 description 2
- RJQXTJLFIWVMTO-TYNCELHUSA-N Methicillin Chemical compound COC1=CC=CC(OC)=C1C(=O)N[C@@H]1C(=O)N2[C@@H](C(O)=O)C(C)(C)S[C@@H]21 RJQXTJLFIWVMTO-TYNCELHUSA-N 0.000 description 2
- KSPIYJQBLVDRRI-UHFFFAOYSA-N N-methylisoleucine Chemical compound CCC(C)C(NC)C(O)=O KSPIYJQBLVDRRI-UHFFFAOYSA-N 0.000 description 2
- 244000061176 Nicotiana tabacum Species 0.000 description 2
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 2
- 102000035195 Peptidases Human genes 0.000 description 2
- 241000255129 Phlebotominae Species 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 108700001094 Plant Genes Proteins 0.000 description 2
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 2
- 239000012979 RPMI medium Substances 0.000 description 2
- 241000270940 Rana temporaria Species 0.000 description 2
- 241001138501 Salmonella enterica Species 0.000 description 2
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
- 241000191940 Staphylococcus Species 0.000 description 2
- 241000193996 Streptococcus pyogenes Species 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
- 239000004473 Threonine Substances 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 2
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 2
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 2
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 2
- 230000021736 acetylation Effects 0.000 description 2
- 238000006640 acetylation reaction Methods 0.000 description 2
- 239000008272 agar Substances 0.000 description 2
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 2
- 230000009435 amidation Effects 0.000 description 2
- 238000007112 amidation reaction Methods 0.000 description 2
- 230000000840 anti-viral effect Effects 0.000 description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
- 235000009582 asparagine Nutrition 0.000 description 2
- 229960001230 asparagine Drugs 0.000 description 2
- 235000003704 aspartic acid Nutrition 0.000 description 2
- 208000022362 bacterial infectious disease Diseases 0.000 description 2
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 229940095731 candida albicans Drugs 0.000 description 2
- 239000006285 cell suspension Substances 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 2
- 235000018417 cysteine Nutrition 0.000 description 2
- 239000000645 desinfectant Substances 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- 210000002257 embryonic structure Anatomy 0.000 description 2
- 229940032049 enterococcus faecalis Drugs 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 235000013922 glutamic acid Nutrition 0.000 description 2
- 239000004220 glutamic acid Substances 0.000 description 2
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 2
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 2
- 239000001630 malic acid Substances 0.000 description 2
- 235000011090 malic acid Nutrition 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 229930182817 methionine Natural products 0.000 description 2
- 229960003085 meticillin Drugs 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 238000010369 molecular cloning Methods 0.000 description 2
- 210000004980 monocyte derived macrophage Anatomy 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 229960001019 oxacillin Drugs 0.000 description 2
- UWYHMGVUTGAWSP-JKIFEVAISA-N oxacillin Chemical compound N([C@@H]1C(N2[C@H](C(C)(C)S[C@@H]21)C(O)=O)=O)C(=O)C1=C(C)ON=C1C1=CC=CC=C1 UWYHMGVUTGAWSP-JKIFEVAISA-N 0.000 description 2
- 230000003071 parasitic effect Effects 0.000 description 2
- 230000001717 pathogenic effect Effects 0.000 description 2
- 238000010647 peptide synthesis reaction Methods 0.000 description 2
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 2
- 230000000704 physical effect Effects 0.000 description 2
- 239000013612 plasmid Substances 0.000 description 2
- 229920001184 polypeptide Polymers 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 235000019833 protease Nutrition 0.000 description 2
- 230000008261 resistance mechanism Effects 0.000 description 2
- 238000004007 reversed phase HPLC Methods 0.000 description 2
- FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 description 2
- 125000006850 spacer group Chemical group 0.000 description 2
- 239000008223 sterile water Substances 0.000 description 2
- 230000009897 systematic effect Effects 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- 238000011200 topical administration Methods 0.000 description 2
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
- 238000011144 upstream manufacturing Methods 0.000 description 2
- 239000004474 valine Substances 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- BVAUMRCGVHUWOZ-ZETCQYMHSA-N (2s)-2-(cyclohexylazaniumyl)propanoate Chemical compound OC(=O)[C@H](C)NC1CCCCC1 BVAUMRCGVHUWOZ-ZETCQYMHSA-N 0.000 description 1
- NPWMTBZSRRLQNJ-VKHMYHEASA-N (3s)-3-aminopiperidine-2,6-dione Chemical compound N[C@H]1CCC(=O)NC1=O NPWMTBZSRRLQNJ-VKHMYHEASA-N 0.000 description 1
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
- AZKSAVLVSZKNRD-UHFFFAOYSA-M 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide Chemical compound [Br-].S1C(C)=C(C)N=C1[N+]1=NC(C=2C=CC=CC=2)=NN1C1=CC=CC=C1 AZKSAVLVSZKNRD-UHFFFAOYSA-M 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- APRZHQXAAWPYHS-UHFFFAOYSA-N 4-[5-[3-(carboxymethoxy)phenyl]-3-(4,5-dimethyl-1,3-thiazol-2-yl)tetrazol-3-ium-2-yl]benzenesulfonate Chemical compound S1C(C)=C(C)N=C1[N+]1=NC(C=2C=C(OCC(O)=O)C=CC=2)=NN1C1=CC=C(S([O-])(=O)=O)C=C1 APRZHQXAAWPYHS-UHFFFAOYSA-N 0.000 description 1
- JDDWRLPTKIOUOF-UHFFFAOYSA-N 9h-fluoren-9-ylmethyl n-[[4-[2-[bis(4-methylphenyl)methylamino]-2-oxoethoxy]phenyl]-(2,4-dimethoxyphenyl)methyl]carbamate Chemical compound COC1=CC(OC)=CC=C1C(C=1C=CC(OCC(=O)NC(C=2C=CC(C)=CC=2)C=2C=CC(C)=CC=2)=CC=1)NC(=O)OCC1C2=CC=CC=C2C2=CC=CC=C21 JDDWRLPTKIOUOF-UHFFFAOYSA-N 0.000 description 1
- 241000589291 Acinetobacter Species 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- 244000144730 Amygdalus persica Species 0.000 description 1
- 108010050820 Antimicrobial Cationic Peptides Proteins 0.000 description 1
- 102000014133 Antimicrobial Cationic Peptides Human genes 0.000 description 1
- 241000228212 Aspergillus Species 0.000 description 1
- 241001561026 Batrachochytrium dendrobatidis Species 0.000 description 1
- 235000016068 Berberis vulgaris Nutrition 0.000 description 1
- 241000335053 Beta vulgaris Species 0.000 description 1
- 241000219477 Bougainvillea glabra Species 0.000 description 1
- 235000003899 Brassica oleracea var acephala Nutrition 0.000 description 1
- 235000011301 Brassica oleracea var capitata Nutrition 0.000 description 1
- 235000001169 Brassica oleracea var oleracea Nutrition 0.000 description 1
- 241000269418 Bufo bufo Species 0.000 description 1
- 125000001433 C-terminal amino-acid group Chemical group 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 244000140995 Capparis spinosa Species 0.000 description 1
- 235000017336 Capparis spinosa Nutrition 0.000 description 1
- 102000005367 Carboxypeptidases Human genes 0.000 description 1
- 108010006303 Carboxypeptidases Proteins 0.000 description 1
- 208000010667 Carcinoma of liver and intrahepatic biliary tract Diseases 0.000 description 1
- 235000005979 Citrus limon Nutrition 0.000 description 1
- 244000248349 Citrus limon Species 0.000 description 1
- HZZVJAQRINQKSD-UHFFFAOYSA-N Clavulanic acid Natural products OC(=O)C1C(=CCO)OC2CC(=O)N21 HZZVJAQRINQKSD-UHFFFAOYSA-N 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 108700010070 Codon Usage Proteins 0.000 description 1
- 244000225789 Cordyline australis Species 0.000 description 1
- 235000001543 Corylus americana Nutrition 0.000 description 1
- 240000007582 Corylus avellana Species 0.000 description 1
- 235000007466 Corylus avellana Nutrition 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- 206010011668 Cutaneous leishmaniasis Diseases 0.000 description 1
- IGXWBGJHJZYPQS-SSDOTTSWSA-N D-Luciferin Chemical compound OC(=O)[C@H]1CSC(C=2SC3=CC=C(O)C=C3N=2)=N1 IGXWBGJHJZYPQS-SSDOTTSWSA-N 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 229920004934 Dacron® Polymers 0.000 description 1
- 235000002767 Daucus carota Nutrition 0.000 description 1
- 244000000626 Daucus carota Species 0.000 description 1
- 206010011906 Death Diseases 0.000 description 1
- CYCGRDQQIOGCKX-UHFFFAOYSA-N Dehydro-luciferin Natural products OC(=O)C1=CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 CYCGRDQQIOGCKX-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 241000255925 Diptera Species 0.000 description 1
- 241000792859 Enema Species 0.000 description 1
- 241000194033 Enterococcus Species 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- BJGNCJDXODQBOB-UHFFFAOYSA-N Fivefly Luciferin Natural products OC(=O)C1CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 BJGNCJDXODQBOB-UHFFFAOYSA-N 0.000 description 1
- 230000005526 G1 to G0 transition Effects 0.000 description 1
- 108700007698 Genetic Terminator Regions Proteins 0.000 description 1
- 229930182566 Gentamicin Natural products 0.000 description 1
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 1
- 241001502121 Glossina brevipalpis Species 0.000 description 1
- DKEXFJVMVGETOO-LURJTMIESA-N Gly-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)CN DKEXFJVMVGETOO-LURJTMIESA-N 0.000 description 1
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 244000299507 Gossypium hirsutum Species 0.000 description 1
- 206010056559 Graft infection Diseases 0.000 description 1
- 244000020551 Helianthus annuus Species 0.000 description 1
- 235000003222 Helianthus annuus Nutrition 0.000 description 1
- 102000001554 Hemoglobins Human genes 0.000 description 1
- 108010054147 Hemoglobins Proteins 0.000 description 1
- 206010073069 Hepatic cancer Diseases 0.000 description 1
- LCWXJXMHJVIJFK-UHFFFAOYSA-N Hydroxylysine Natural products NCC(O)CC(N)CC(O)=O LCWXJXMHJVIJFK-UHFFFAOYSA-N 0.000 description 1
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 1
- 206010020649 Hyperkeratosis Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 241000588748 Klebsiella Species 0.000 description 1
- SNDPXSYFESPGGJ-BYPYZUCNSA-N L-2-aminopentanoic acid Chemical compound CCC[C@H](N)C(O)=O SNDPXSYFESPGGJ-BYPYZUCNSA-N 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- SNDPXSYFESPGGJ-UHFFFAOYSA-N L-norVal-OH Natural products CCCC(N)C(O)=O SNDPXSYFESPGGJ-UHFFFAOYSA-N 0.000 description 1
- LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
- 231100000111 LD50 Toxicity 0.000 description 1
- 241000122138 Leishmania arabica Species 0.000 description 1
- 241000346663 Leishmania colombiensis Species 0.000 description 1
- 241001260751 Leishmania equatorensis Species 0.000 description 1
- 241000222697 Leishmania infantum Species 0.000 description 1
- 241000222703 Leishmania shawi Species 0.000 description 1
- 241001137872 Leishmania sp. Species 0.000 description 1
- OJMMVQQUTAEWLP-UHFFFAOYSA-N Lincomycin Natural products CN1CC(CCC)CC1C(=O)NC(C(C)O)C1C(O)C(O)C(O)C(SC)O1 OJMMVQQUTAEWLP-UHFFFAOYSA-N 0.000 description 1
- 235000004431 Linum usitatissimum Nutrition 0.000 description 1
- 240000006240 Linum usitatissimum Species 0.000 description 1
- 241000760056 Lithoglyptes ivanovi Species 0.000 description 1
- DDWFXDSYGUXRAY-UHFFFAOYSA-N Luciferin Natural products CCc1c(C)c(CC2NC(=O)C(=C2C=C)C)[nH]c1Cc3[nH]c4C(=C5/NC(CC(=O)O)C(C)C5CC(=O)O)CC(=O)c4c3C DDWFXDSYGUXRAY-UHFFFAOYSA-N 0.000 description 1
- 239000006142 Luria-Bertani Agar Substances 0.000 description 1
- 239000006137 Luria-Bertani broth Substances 0.000 description 1
- 235000007688 Lycopersicon esculentum Nutrition 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 244000081841 Malus domestica Species 0.000 description 1
- 235000011430 Malus pumila Nutrition 0.000 description 1
- 235000015103 Malus silvestris Nutrition 0.000 description 1
- 240000004658 Medicago sativa Species 0.000 description 1
- 235000017587 Medicago sativa ssp. sativa Nutrition 0.000 description 1
- 102000008109 Mixed Function Oxygenases Human genes 0.000 description 1
- 108010074633 Mixed Function Oxygenases Proteins 0.000 description 1
- OLNLSTNFRUFTLM-UHFFFAOYSA-N N-ethylasparagine Chemical compound CCNC(C(O)=O)CC(N)=O OLNLSTNFRUFTLM-UHFFFAOYSA-N 0.000 description 1
- YPIGGYHFMKJNKV-UHFFFAOYSA-N N-ethylglycine Chemical compound CC[NH2+]CC([O-])=O YPIGGYHFMKJNKV-UHFFFAOYSA-N 0.000 description 1
- 108010065338 N-ethylglycine Proteins 0.000 description 1
- AKCRVYNORCOYQT-YFKPBYRVSA-N N-methyl-L-valine Chemical compound CN[C@@H](C(C)C)C(O)=O AKCRVYNORCOYQT-YFKPBYRVSA-N 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 108010038807 Oligopeptides Proteins 0.000 description 1
- 102000015636 Oligopeptides Human genes 0.000 description 1
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 206010034133 Pathogen resistance Diseases 0.000 description 1
- 241000517710 Pelophylax Species 0.000 description 1
- 241000270936 Pelophylax esculentus Species 0.000 description 1
- 101000801485 Pelophylax saharicus Temporin-SHa Proteins 0.000 description 1
- 208000037581 Persistent Infection Diseases 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 244000018633 Prunus armeniaca Species 0.000 description 1
- 235000009827 Prunus armeniaca Nutrition 0.000 description 1
- 235000006040 Prunus persica var persica Nutrition 0.000 description 1
- 241000589516 Pseudomonas Species 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 108091030066 RNAIII Proteins 0.000 description 1
- 241000270930 Rana japonica Species 0.000 description 1
- 108700008625 Reporter Genes Proteins 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 240000000528 Ricinus communis Species 0.000 description 1
- 235000004443 Ricinus communis Nutrition 0.000 description 1
- 240000000111 Saccharum officinarum Species 0.000 description 1
- 235000007201 Saccharum officinarum Nutrition 0.000 description 1
- 241000607142 Salmonella Species 0.000 description 1
- 108010077895 Sarcosine Proteins 0.000 description 1
- 240000000840 Solanum erianthum Species 0.000 description 1
- 235000003161 Solanum erianthum Nutrition 0.000 description 1
- 241001198427 Solanum laxum Species 0.000 description 1
- 235000018694 Solanum laxum Nutrition 0.000 description 1
- 240000003768 Solanum lycopersicum Species 0.000 description 1
- 241000201932 Solanum villosum Species 0.000 description 1
- 235000013156 Solanum villosum Nutrition 0.000 description 1
- 241000194017 Streptococcus Species 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- WKDDRNSBRWANNC-UHFFFAOYSA-N Thienamycin Natural products C1C(SCCN)=C(C(O)=O)N2C(=O)C(C(O)C)C21 WKDDRNSBRWANNC-UHFFFAOYSA-N 0.000 description 1
- 108700019146 Transgenes Proteins 0.000 description 1
- 235000021307 Triticum Nutrition 0.000 description 1
- 244000098338 Triticum aestivum Species 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 241000223105 Trypanosoma brucei Species 0.000 description 1
- 241000223109 Trypanosoma cruzi Species 0.000 description 1
- 241000223095 Trypanosoma evansi Species 0.000 description 1
- 241000223099 Trypanosoma vivax Species 0.000 description 1
- 206010052664 Vascular shunt Diseases 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 230000003187 abdominal effect Effects 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 239000012872 agrochemical composition Substances 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000002862 amidating effect Effects 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 229940124277 aminobutyric acid Drugs 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 229960000723 ampicillin Drugs 0.000 description 1
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 1
- 239000003994 anesthetic gas Substances 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 244000037640 animal pathogen Species 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000000507 anthelmentic effect Effects 0.000 description 1
- 230000002924 anti-infective effect Effects 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 210000004507 artificial chromosome Anatomy 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 230000001746 atrial effect Effects 0.000 description 1
- 229960004099 azithromycin Drugs 0.000 description 1
- MQTOSJVFKKJCRP-BICOPXKESA-N azithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)N(C)C[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 MQTOSJVFKKJCRP-BICOPXKESA-N 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229940027138 cambia Drugs 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 229960000603 cefalotin Drugs 0.000 description 1
- VAAUVRVFOQPIGI-SPQHTLEESA-N ceftriaxone Chemical compound S([C@@H]1[C@@H](C(N1C=1C(O)=O)=O)NC(=O)\C(=N/OC)C=2N=C(N)SC=2)CC=1CSC1=NC(=O)C(=O)NN1C VAAUVRVFOQPIGI-SPQHTLEESA-N 0.000 description 1
- 230000006037 cell lysis Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 238000001516 cell proliferation assay Methods 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 239000004568 cement Substances 0.000 description 1
- VUFGUVLLDPOSBC-XRZFDKQNSA-M cephalothin sodium Chemical compound [Na+].N([C@H]1[C@@H]2N(C1=O)C(=C(CS2)COC(=O)C)C([O-])=O)C(=O)CC1=CC=CS1 VUFGUVLLDPOSBC-XRZFDKQNSA-M 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 230000003399 chemotactic effect Effects 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 229960003405 ciprofloxacin Drugs 0.000 description 1
- 229960003324 clavulanic acid Drugs 0.000 description 1
- HZZVJAQRINQKSD-PBFISZAISA-N clavulanic acid Chemical compound OC(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21 HZZVJAQRINQKSD-PBFISZAISA-N 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 229960002227 clindamycin Drugs 0.000 description 1
- KDLRVYVGXIQJDK-AWPVFWJPSA-N clindamycin Chemical compound CN1C[C@H](CCC)C[C@H]1C(=O)N[C@H]([C@H](C)Cl)[C@@H]1[C@H](O)[C@H](O)[C@@H](O)[C@@H](SC)O1 KDLRVYVGXIQJDK-AWPVFWJPSA-N 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 230000005757 colony formation Effects 0.000 description 1
- 238000004737 colorimetric analysis Methods 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 238000002784 cytotoxicity assay Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- YSMODUONRAFBET-UHFFFAOYSA-N delta-DL-hydroxylysine Natural products NCC(O)CCC(N)C(O)=O YSMODUONRAFBET-UHFFFAOYSA-N 0.000 description 1
- 208000002925 dental caries Diseases 0.000 description 1
- 239000004053 dental implant Substances 0.000 description 1
- 230000000249 desinfective effect Effects 0.000 description 1
- 238000003795 desorption Methods 0.000 description 1
- KXZOIWWTXOCYKR-UHFFFAOYSA-M diclofenac potassium Chemical compound [K+].[O-]C(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl KXZOIWWTXOCYKR-UHFFFAOYSA-M 0.000 description 1
- 231100000676 disease causative agent Toxicity 0.000 description 1
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 1
- 229960003722 doxycycline Drugs 0.000 description 1
- XQTWDDCIUJNLTR-CVHRZJFOSA-N doxycycline monohydrate Chemical compound O.O=C1C2=C(O)C=CC=C2[C@H](C)[C@@H]2C1=C(O)[C@]1(O)C(=O)C(C(N)=O)=C(O)[C@@H](N(C)C)[C@@H]1[C@H]2O XQTWDDCIUJNLTR-CVHRZJFOSA-N 0.000 description 1
- 229940000406 drug candidate Drugs 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000007920 enema Substances 0.000 description 1
- 229940095399 enema Drugs 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 230000008029 eradication Effects 0.000 description 1
- YSMODUONRAFBET-UHNVWZDZSA-N erythro-5-hydroxy-L-lysine Chemical compound NC[C@H](O)CC[C@H](N)C(O)=O YSMODUONRAFBET-UHNVWZDZSA-N 0.000 description 1
- 229960003276 erythromycin Drugs 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 210000000416 exudates and transudate Anatomy 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- 210000003953 foreskin Anatomy 0.000 description 1
- 238000012395 formulation development Methods 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 229960002518 gentamicin Drugs 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 108010050848 glycylleucine Proteins 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 210000003709 heart valve Anatomy 0.000 description 1
- 229940025294 hemin Drugs 0.000 description 1
- BTIJJDXEELBZFS-QDUVMHSLSA-K hemin Chemical compound CC1=C(CCC(O)=O)C(C=C2C(CCC(O)=O)=C(C)\C(N2[Fe](Cl)N23)=C\4)=N\C1=C/C2=C(C)C(C=C)=C3\C=C/1C(C)=C(C=C)C/4=N\1 BTIJJDXEELBZFS-QDUVMHSLSA-K 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 210000004408 hybridoma Anatomy 0.000 description 1
- QJHBJHUKURJDLG-UHFFFAOYSA-N hydroxy-L-lysine Natural products NCCCCC(NO)C(O)=O QJHBJHUKURJDLG-UHFFFAOYSA-N 0.000 description 1
- 229960002591 hydroxyproline Drugs 0.000 description 1
- 229960002182 imipenem Drugs 0.000 description 1
- ZSKVGTPCRGIANV-ZXFLCMHBSA-N imipenem Chemical compound C1C(SCC\N=C\N)=C(C(O)=O)N2C(=O)[C@H]([C@H](O)C)[C@H]21 ZSKVGTPCRGIANV-ZXFLCMHBSA-N 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000010874 in vitro model Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 210000005007 innate immune system Anatomy 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 150000003951 lactams Chemical group 0.000 description 1
- 239000004816 latex Substances 0.000 description 1
- 229920000126 latex Polymers 0.000 description 1
- 231100000636 lethal dose Toxicity 0.000 description 1
- OJMMVQQUTAEWLP-KIDUDLJLSA-N lincomycin Chemical compound CN1C[C@H](CCC)C[C@H]1C(=O)N[C@H]([C@@H](C)O)[C@@H]1[C@H](O)[C@H](O)[C@@H](O)[C@@H](SC)O1 OJMMVQQUTAEWLP-KIDUDLJLSA-N 0.000 description 1
- 229960005287 lincomycin Drugs 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 201000002250 liver carcinoma Diseases 0.000 description 1
- 238000004020 luminiscence type Methods 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 210000001161 mammalian embryo Anatomy 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000007769 metal material Substances 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 239000006994 mh medium Substances 0.000 description 1
- 238000000520 microinjection Methods 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 230000008811 mitochondrial respiratory chain Effects 0.000 description 1
- 238000001823 molecular biology technique Methods 0.000 description 1
- 201000000626 mucocutaneous leishmaniasis Diseases 0.000 description 1
- 210000004897 n-terminal region Anatomy 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- 230000000399 orthopedic effect Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- FHFYDNQZQSQIAI-UHFFFAOYSA-N pefloxacin Chemical compound C1=C2N(CC)C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CCN(C)CC1 FHFYDNQZQSQIAI-UHFFFAOYSA-N 0.000 description 1
- 229960004236 pefloxacin Drugs 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 230000008823 permeabilization Effects 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 210000004180 plasmocyte Anatomy 0.000 description 1
- 239000011505 plaster Substances 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 239000005020 polyethylene terephthalate Substances 0.000 description 1
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 1
- 239000004810 polytetrafluoroethylene Substances 0.000 description 1
- 229920002635 polyurethane Polymers 0.000 description 1
- 239000004814 polyurethane Substances 0.000 description 1
- 230000001323 posttranslational effect Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- XJMOSONTPMZWPB-UHFFFAOYSA-M propidium iodide Chemical compound [I-].[I-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CCC[N+](C)(CC)CC)=C1C1=CC=CC=C1 XJMOSONTPMZWPB-UHFFFAOYSA-M 0.000 description 1
- 235000019419 proteases Nutrition 0.000 description 1
- 210000001938 protoplast Anatomy 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 238000000611 regression analysis Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- JQXXHWHPUNPDRT-WLSIYKJHSA-N rifampicin Chemical compound O([C@](C1=O)(C)O/C=C/[C@@H]([C@H]([C@@H](OC(C)=O)[C@H](C)[C@H](O)[C@H](C)[C@@H](O)[C@@H](C)\C=C\C=C(C)/C(=O)NC=2C(O)=C3C([O-])=C4C)C)OC)C4=C1C3=C(O)C=2\C=N\N1CC[NH+](C)CC1 JQXXHWHPUNPDRT-WLSIYKJHSA-N 0.000 description 1
- 229960001225 rifampicin Drugs 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 230000009919 sequestration Effects 0.000 description 1
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
- 229920002379 silicone rubber Polymers 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 230000010473 stable expression Effects 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 229920001169 thermoplastic Polymers 0.000 description 1
- 239000004416 thermosoftening plastic Substances 0.000 description 1
- YSMODUONRAFBET-WHFBIAKZSA-N threo-5-hydroxy-L-lysine Chemical compound NC[C@@H](O)CC[C@H](N)C(O)=O YSMODUONRAFBET-WHFBIAKZSA-N 0.000 description 1
- 229960000707 tobramycin Drugs 0.000 description 1
- NLVFBUXFDBBNBW-PBSUHMDJSA-N tobramycin Chemical compound N[C@@H]1C[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N NLVFBUXFDBBNBW-PBSUHMDJSA-N 0.000 description 1
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 230000005945 translocation Effects 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 239000007222 ypd medium Substances 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/463—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from amphibians
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Toxicology (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Zoology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Virology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Breeding Of Plants And Reproduction By Means Of Culturing (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Materials For Medical Uses (AREA)
Abstract
Description
F−L−K−G−I−K−G−M−L−G−K−L−F(配列番号:3);
F−L−K−G−I−V−G−K−L−G−K−L−F(配列番号:4);
F−L−K−G−I−V−G−M−L−G−K−L−L(配列番号:5);
F−L−K−G−I−V−G−M−L−G−K−L−W(配列番号:6);
F−L−K−G−I−V−G−M−L−G−K−L−I(配列番号:7);
F−L−K−G−I−K−G−M−L−G−K−L−L(配列番号:8);
F−L−K−G−I−K−G−M−L−G−K−L−W(配列番号:9);
F−L−K−G−I−K−G−M−L−G−K−L−I(配列番号:10);
F−L−K−G−I−V−G−K−L−G−K−L−W(配列番号:11);
F−L−K−G−I−V−G−K−L−G−K−L−L(配列番号:12);
F−L−K−G−I−V−G−K−L−G−K−L−I(配列番号:13);
F−L−K−G−I−K−G−K−L−G−K−L−F(配列番号:14);
F−L−K−G−I−K−G−K−L−G−K−L−L(配列番号:15);
F−L−K−G−I−K−G−K−L−G−K−L−W(配列番号:16);および
F−L−K−G−I−K−G−K−L−G−K−L−I(配列番号:17)
からなる群より選択される配列を含む、または該配列からなるペプチドからなる群より選択されてもよい。
本明細書において、「ペプチド」、「オリゴペプチド」、「ポリペプチド」および「タンパク質」なる語は、互換的に利用され、ペプチド結合により連結したアミノ酸の鎖をいい、その鎖を形成するアミノ酸の数は関係ない。
F−L−X1−G−I−X2−G−M−L−G−K−L−F(配列番号:18)、
F−L−X1−G−I−V−G−X3−L−G−K−L−F(配列番号:19)、
F−L−X1−G−I−V−G−M−L−G−K−L−X4(配列番号:20)、
F−L−X1−G−I−X2−G−X3−L−G−K−L−F(配列番号:21)、
F−L−X1−G−I−X2−G−M−L−G−K−L−X4(配列番号:22)、
F−L−X1−G−I−V−G−X3−L−G−K−L−X4(配列番号:23)および
F−L−X1−G−I−X2−G−X3−L−G−K−L−X4(配列番号:2)
(ここで、X1、X2およびX3は、同一または異なり、R、HおよびKからなる群より選択され、そしてX4はI、LおよびWからなる群より、好ましくはLおよびWからなる群より選択される)
からなる群より選択される配列を含むか、または該配列からなる。
F−L−K−G−I−K−G−M−L−G−K−L−F(配列番号:3)、
F−L−K−G−I−V−G−K−L−G−K−L−F(配列番号:4)、
F−L−K−G−I−V−G−M−L−G−K−L−L(配列番号:5)、
F−L−K−G−I−V−G−M−L−G−K−L−W(配列番号:6)、
F−L−K−G−I−V−G−M−L−G−K−L−I(配列番号:7)、
F−L−K−G−I−K−G−M−L−G−K−L−L(配列番号:8)、
F−L−K−G−I−K−G−M−L−G−K−L−W(配列番号:9)、
F−L−K−G−I−K−G−M−L−G−K−L−I(配列番号:10)、
F−L−K−G−I−V−G−K−L−G−K−L−W(配列番号:11)、
F−L−K−G−I−V−G−K−L−G−K−L−L(配列番号:12)、
F−L−K−G−I−V−G−K−L−G−K−L−I(配列番号:13)、
F−L−K−G−I−K−G−K−L−G−K−L−F(配列番号:14)、
F−L−K−G−I−K−G−K−L−G−K−L−L(配列番号:15)、
F−L−K−G−I−K−G−K−L−G−K−L−W(配列番号:16)および
F−L−K−G−I−K−G−K−L−G−K−L−I (配列番号:17)
からなる群より選択される配列を含むか、または該配列からなる。
より好ましくは、該ペプチドは、配列番号:3〜6および8の配列からなる群より選択される配列を含むか、または該配列からなり、さらにより好ましくは、配列番号:3、5および6の配列からなる群より選択される配列を含むか、または該配列からなる。
材料および方法
固相ペプチド合成
固相ペプチド合成は、Vanhoyeら(Vanhoyeら、2004)によって記載されるプロトコルに従い、Fmoc保護アミノ酸(Novabiochem, Switzerland)およびRinkアミドMBHA樹脂(Senn Chemicals, Switzerland)を利用することにより、自動ペプチド合成装置(Applied Biosystems 433A)を用いて実施された。
次の菌株:エシェリキア・コリ(ATCC25922およびML−35p)、スタフィロコッカス・アウレウス(ATCC25923およびST1065)、エンテロコッカス・フェカリス(ATCC29212)、シュードモナス・エルギノーサ(ATCC27853)、ストレプトコッカス・ピオゲネス(ATCC19615)、リステリア・イバノビ、サルモネラ・エンテリカ(血清型エンテリディディス)、アシネトバクター・バウマンニ(ATCC19606)およびクラブシエラ・ニューモニエ(ATCC13883)を抗微生物活性の試験に用いた。2種の抗生物質耐性菌株(エス・アウレウスATCC43300およびATCCBAA−44)も用いた。
3種の酵母菌株:サッカロミセス・セレビシア、カンジダ・アルビカンス(ATCC90028)、カンジダ・パラシローシス(ATCC22019)を試験した。これらの菌株を最初にYPD寒天上で最低48時間増殖させた。次に酵母懸濁液を、YPDブロス培地中で、細菌が106cfu/mLに正確に調整されるように、調製した。
ペプチドのリーシュマニア活性は、内臓リーシュマニア症に関与する、前鞭毛型の小児リーシュマニア(菌株 MHOM/MA/67/ITMAP−263)について評価された。
80μLの前鞭毛虫懸濁液(105寄生虫/ウェル)を20μLのペプチド溶液(50ないし3.125μMの最終濃度)と一緒にマイクロタイタープレートの各ウェルにアリコートした。負の対照では、ペプチド溶液を20μLのSDM79培地と置き換えた。正の対照では、20μLの溶液の代わりに最高濃度のペプチドを用いて実施された。実験は各ペプチド濃度で3回重複して行われた。
増殖%=[(L平均値−bgd)ペプチドx100]/(L平均値−bgd)負の対照
(ここで、「L平均値」は平均蛍光値を、そして「bgd」は培地により発せされる蛍光に相当するバックグラウンドでの蛍光値を意味する)
に従って算定した。前鞭毛虫の増殖を50%まで阻害する濃度(IC50)を決定した。
抗微生物ペプチドの細胞毒性活性を、ラット赤血球、ヒト白血病単球細胞株のTHP−1、THP−1単球誘導のマクロファージについて、HepG2のヒト肝がん誘導細胞(ヒト肝がん由来細胞株)およびヒト線維芽細胞について確かめた。マクロファージはリーシュマニアの宿主細胞である。
抗微生物ペプチドの溶血活性をラット赤血球を用いて評価した。赤血球溶血はヘモグロビンの反応媒体への放出により明らかにされ、その濃度は450nmで分光光度的に測定される。
細胞を、指数増殖期に達するまで、RPMI培地(10%FCS、1/100グルタマックス(登録商標)(Invitrogen)および100U/mLのペニシリン、100μg/mLのストレプトマイシン)にて培養した。トーマ(Thoma)計数チャンバーにて計数した後、RPMI1640培地中で細胞密度を6.25x105細胞/mLに調整した。5倍に濃縮した抗微生物ペプチドの溶液をこのRPMI培地中で調製した(250〜15.6μM)。
増殖%=[(OD平均値−bgd)ペプチドx100]/(OD平均値−bgd)負の対照
(ここで、「bgd」は培地による吸光度に相当するバックグラウンドでのODを意味する)
で示されるように算定された。負の対照(100%増殖)はペプチドを含有しなかった。
マクロファージの生存能をトリパンブルーをベースとするミクロアッセイを用いて確かめた。中間対数増殖期にある培養懸濁液からのTHP−1細胞を96ウェルプレートに5x105細胞/mLの密度(100μL/ウェル、すなわち5x104細胞/ウェル)でプレートし、上記されるように分化させた。ペプチド(60μM〜7.5μM、最終濃度)の存在下、37℃で5%CO2と共に72時間インキュベートした後、接着したマクロファージを予め暖めたRPMI1640培地で一度に洗浄し、RPMI1640培地に2倍に希釈した100μLのトリパンブルーで5分間染色させた。網目状接眼レンズを用いてウェルに付き3つに焦点を当てて生存白血球を顕微鏡により計数した。
VI=[N平均値ペプチドx100]/N平均値負の対照
(ここで、N平均値は生存する寄生虫の平均数である)
を用いて各ペプチド濃度について算定した。負の対照(100%増殖)は20μLのRPMI1640培地を該ペプチド溶液の代わりに含有した。
HepG2ヒト肝細胞がん誘導の細胞を96ウェルプレート上の10%の補体除去したウシ胎児血清、1/100グルタマックス(登録商標)(Invitrogen)および100IUのペニシリン/mL、および100μgのストレプトマイシン/mLを補足したMEM培地に5x105細胞/mLの密度で播種し、37℃および5%CO2で72時間増殖かつ接着させた。連続希釈したペプチドを100μLの補足MEM培地に添加した(100μM〜600μM)。72時間インキュベートした後、ヒト単球のTHP−1について上記されるのと同様にしてMTTベースのマイクロアッセイを用いて細胞生存能を評価した。
ヒト包皮線維芽細胞を、10%ウシ胎児血清(FBS;Invitrogen)、4mMグルタミン、500U/mlのペニシリン、および250μg/mlのストレプトマイシンを補足したダルベコ修飾イーグル培地(DMEM;Invitrogen)にて、37℃で5%CO2下で培養した。104細胞/ウェル(96ウェルプレート)を播種した。24時間後、連続希釈したペプチドを添加し、72時間後の増殖期に、テトラゾリウム化合物の(3-(4,5-ジメチルチアゾール-2-イル)-5-(3-カルボキシメトキシフェニル)-2-(4-スルホフェニル)-2H-テトラゾリウム)を培養ウェルに直接添加した。生存細胞により産生されたホルマザンの生体内還元された色相を96ウェルプレートのリーダー(吸光度、490nm)で定量した。LC50は非線形回帰分析により決定された。
それらの物理化学的特性に基づき、テンポリンSHaの一連の欠失または置換されたアナログを設計して強力な抗微生物活性および細胞毒性の減少を得た(図2)。これらのアナログの抗微生物活性は、異なるグラム陽性菌、グラム陰性菌、および抗生物質耐性菌の参考菌株について、および真菌株について評価された。
その結果は、[K3]テンポリンSHaは、グラム陽性菌株(抗生物質耐性のエス・アウレウス菌株を含む)および臨床的に関心のあるグラム陰性菌株、ならびに酵母に対して同じ効能(MIC=3−6μM)で作用する強力な広域スペクトルの抗微生物剤である(図4)。[K3]テンポリンSHaの配列での2個の残基の内部欠失(残基V6およびM8の欠失)およびC−末端切断は該ペプチドを不活化する(図示せず):ただし、[K3]テンポリンSHa(3−13)はグラム陽性菌およびグラム陰性菌に対する活性を保存する(図4)。興味のあることに、このN−末端切断したアナログは酵母(シー・アルビカンスおよびシー・パラプシローシス)に対して、およびピー・アエルギノーザ(大多数のテンポリンに対して耐性を示すグラム陰性菌株)に対してテンポリンSHaと比べて2倍の活性を示し、その溶血活性も喪失している(LC50=618μM)。[K3]テンポリンSHa(3−13)と同様の物理化学特性を有する、C−末端切断したアナログの[K3]テンポリンSHa(1−11)で活性のないことは、テンポリンSHaのC−末端の疎水性鎖が抗微生物活性に必要不可欠であることを示す。N−末端およびC−末端切断したアナログの[K3]テンポリンSHa(3−11)もまた不活性であるということはC−末端の重要性を確認するものである。
テンポリンSHaの置換したすべてのアナログは、小児リーシュマニアの前鞭毛虫に対してその活性が様々な程度で減少し、アナログ[K3,K6]、[K3,K8]および[K3,K6,L13]テンポリンSHaでは単球に対する細胞毒性レベルが接近している。細菌の場合、アナログ[K3,L13]および[K3,W13]の抗リーシュマニア活性はあまり変わらない。
テンポリンSHaおよびそのアナログは、原核生物であるグラム陽性およびグラム陰性菌、ならびに真核生物である酵母の増殖を予防しうるため、広域スペクトルの活性を示す。
Abbassi F、Oury B、Blasco T、Sereno D、Bolbach G、Nicolas P、Hani K、Amiche M、Ladram A (2008)「北アフリカのアカガエル、Pelophylax saharicaの皮膚からの新規なテンポリンの単離、特徴化および分子クローニング」Peptides 29:1526-33;
Abbassi F、Raja Z、Oury B、Gazanion E、Piesse C、Sereno D、Nicolas P、Foulon T、Ladram A (2013)「テンポリンSHd、17残基長の膜障害ペプチドの抗菌およびリーシュマニア活性」Biochimie 95:388-99;
Abbassi F、Lequin O、Piesse C、Goasdoue N、Foulon T、Nicolas P、Ladram A (2010)「テンポリンSHf、新規な型のpheに富み、疎水性の超短い抗微生物ペプチド」J Biol Chem 285:16880-92;
Brun R、Schonenberger M (1979)「トリパノソーマ・ブルセイの半規定培地での培養、およびインビトロクローニングまたはプロサイクリックカルチャー形態」Acta Trop. 36:289-92;
Bevan M (1984)「植物の形質転換用のバイナリー・アグロバクテリウム・ベクター」Nucleic Acids Res. 12:8711-21;
Camargo, E. P. 1964.「トリパノソーマ・クルージの増殖および分化:液体培地での発育終末トリパノソーマのI起源」Rev. Instit. Med. Trop. Sao Paulo 6:93-100;
Chinchar VG、Bryan L、Silphadaung U、Noga E、Wade D、Rollins-Smith L (2004)「両生類および魚類のペプチドによる外温性動物に感染するウイルスの不活化」Virology 323:268-75;
Cirioni O、Giacometti A、Ghiselli R、Dell Acqua G、Gov Y、Kamysz W、Lukasiak J、Mocchegiani F、Orlando F、DAmato G、Balaban N、Saba V、Scalise G (2003)「糖タンパク質に対して中程度の耐性を有するスタフィロコッカスに起因するグラフト感染の皮下ラットパウチ(Pouch)モデルにおける局所的テンポリンAおよびRNAIIIを阻害するペプチドの予防的効能」Circulation 108:767-71;
Conlon JM (2008)「アカガエル科のカエルの皮膚から由来の抗微生物ペプチドの系統的学術名に対するリフレクション」Peptides 29:1815-9;
Conlon JM、Kolodziejek J、Nowotny N (2009)「北アメリカのカエルの皮膚から由来の抗微生物ペプチド」Biochim. Biophys. Acta, 1788:1556-63;
Cunningham, I.、1977.「ツェツェバエ組織の維持およびトリパノソーマ類の増殖のための新規な培地」J. Protozool. 24:325-329;
Dennison SR、Wallace J、Harris F、Phoenix DA (2005)「両親媒性α−ヘリカル抗微生物ペプチドおよびその構造/機能の関係」Protein Pept. Lett. 12:31-9;
Giangaspero A、Sandri L、Tossi A (2001)「両親媒性α−ヘリカル抗微生物ペプチド:生物活性におけるその構造的および物理的特性の効果の系統的研究」Eur. J. Biochem. 268:5589-600;
Hajdukiewicz P、Svab Z、Maliga P (1994)「植物の形質転換用の小型で万能なpPZPファミリーのアグロバクテリウム・バイナリーベクター」Plant Mol. Biol. 25:989-94;
Hooykaas PJJ、Schilperoort RA (1992)「アグロバクテリウムおよび植物の遺伝子操作」Plant Mol. Biol. 19:15-38;
Isaacson T、Soto A、Iwamuro S、Knoop FC、Conlon JM (2002)「ジャパニーズ・マウンテン・ブラウン・フロッグ、Rana ornativentrisの皮膚からの不定型の構造的特徴を有する抗微生物ペプチド」Peptides 23:419-25;
Kim JB、Iwamuro S、Knoop FC、Conlon JM (2001)「ジャパニーズ・マウンテン・ブラウン・フロッグ、Rana ornativentrisの皮膚から由来の抗微生物ペプチド」J. Pept. Res. 58:349-56;
Kullmann W (1987)「酵素によるペプチド合成」CRC Press, Florida;
Lemesre, J-L.、D. Sereno、S. Daulouede、B. Veyret、N. BrajonおよびP. Vincendeau. 1997.「リーシュマニア・スピーシズ:前鞭毛型および無菌状態で増殖させた無前鞭毛型の一酸化窒素介在性代謝阻害」Exp. Parasitol. 86:58-68;
Mangoni ML (2006)「テンポリン、エクスパンディング特性を有する抗感染性ペプチド」Cell. Mol. Life Sci. 63:1060-9;
Mosmann T (1983)「細胞の増殖および生存についての迅速な比色分析:増殖および細胞傷害アッセイへの応用」J. Immunol. Methods 65:55-63;
Rollins-Smith LA、Carey C、Conlon JM、Reinert LK、Doersam JK、Bergman Tら (2003)「両生類のグローバルな退歩と関連付けられるツボカビ真菌(Batrachochytrium dendrobatidis)に対するテンポリンファミリーペプチドの活性」Antimicrob. Agents Chemother. 47:1157-60;
Roy G、Dumas C、Sereno D、Wu Y、Singh AK、Tremblay MJ、Ouellette M、Olivier M、Papadopoulou B (2000)「マクロファージにおける、および動物実験におけるリーシュマニア・スピーシズ感染を定量するためのルシフェラーゼ受容体遺伝子のエピソームおよび安定した発現」Mol. Biochem. Parasitol. 110:195-206;
Russell JA、Roy MK、Sanford JC (1992)「浮遊培養したタバコ細胞の遺伝子銃による形質転換における大幅な改善」In Vitro Cell. Dev. Biol., 28P, p. 97-105;
Sambrook J, Russell D (2001) モレキュラー・クローニング:実験室マニュアル、第3版、Cold Spring Harbor;
Sereno D, Lemesre JL (1997)「リーシュマニア拮抗剤の研究のためにインビトロモデルとして無菌状態で培養した無鞭毛型」Antimicrob. Agents Chemother. 41:972-6;
Siemens, J、Schieder O (1996)「トランスジェニック植物:新しい展開および最先端の遺伝形質転換」Plant Tissue Cult. Biotechnol. 2:66-75;
Simmaco M、De Biase G、Severini C、Aita M、Falconieri G、Erspamer、Barra D、Bossa F (1990)「ヨーロッパトノサマガエルの皮膚抽出物から由来の生物活性ペプチドの精製および特徴付け」Biochem. Biophys. Acta 1033:318-23;
Simmaco M、Mignogna G、Canofeni S、Miele R、Mangoni ML、Barra D (1996)「テンポリン、ヨーロピアン・レッド・フロッグ、Rana temporariaから由来の抗微生物ペプチド」Eur. J. Biochem. 242:788-92;
Vanhoye D、Bruston F、El Amri S、Ladram A、Amiche M、Nicolas P (2004)「異なる機能のGly−Leuに富むペプチドオーソログの膜会合、静電気隔離および細胞毒性」Biochemistry 43:8391-409;
Yeaman MR、Yount NY (2003)「抗微生物ペプチドの作用および耐性の機構」Pharmacol. Rev. 55:27-55;
Claims (15)
- 13〜100個のアミノ酸からなる大きさのペプチドであって、抗微生物活性を示し、配列:F−L−X1−G−I−X2−G−X3−L−G−K−L−X4(配列番号:2)
ここで、
X1はR、HおよびKからなる群より選択されるアミノ酸であり;
X2はV、R、HおよびKからなる群より選択されるアミノ酸であり;
X3はM、R、HおよびKからなる群より選択されるアミノ酸であり;および
X4はF、I、LおよびWからなる群より選択されるアミノ酸である:
ただしX2がVである場合、その時にはX3はK、RおよびHからなる群より選択され、および/またはX4はL、IおよびWからなる群より選択される
を含むペプチド、ならびに該ペプチドの機能的誘導体および医薬的に許容される塩。 - X1がKを表し、X2がVおよびKからなる群より選択されるアミノ酸であり、X3がMおよびKからなる群より選択されるアミノ酸であり、X4がF、LおよびWからなる群より選択されるアミノ酸である、請求項1に記載のペプチド。
- 配列番号3〜17の配列からなる群より選択される配列、好ましくは配列番号:3〜6、8、9、11、12および14〜16の配列からなる群より選択される配列、より好ましくは配列番号:3〜6および8の配列からなる群より選択される配列を含むか、または該配列からなる、請求項1または2に記載のペプチド。
- 請求項1〜3のいずれか一項に記載のペプチドをコードする核酸。
- 請求項4に記載の核酸を含む発現カセット。
- 請求項4に記載の核酸または請求項5に記載の発現カセットを含む発現ベクター。
- 請求項4に記載の核酸、請求項5に記載の発現カセット、または請求項6に記載の発現ベクターを含む宿主細胞。
- 請求項1〜3のいずれか一項に記載の少なくとも1つのペプチド、および医薬的に許容される支持体および/または賦形剤を含む医薬組成物。
- 薬剤としての請求項1〜3のいずれか一項に記載のペプチド。
- 薬剤が細菌、ウイルス、真菌または寄生虫による感染を治療するものとする、請求項9に記載のペプチド。
- 寄生虫がリーシュマニア属に属する、請求項10に記載のペプチド。
- 微生物感染の治療における使用のための、請求項1〜3のいずれか一項に記載に記載のペプチド、請求項4に記載の核酸、請求項5に記載の発現カセット、または請求項6に記載のベクター。
- 請求項1〜3のいずれか一項に記載のペプチドの、殺菌剤、保存剤または殺虫剤としての使用。
- 請求項1〜3のいずれか一項に記載のペプチドで被覆されるか、または該ペプチドを含む少なくとも1つの表面を有する本体を含む医療装置またはインプラント。
- 請求項4に記載の核酸、請求項5に記載の発現カセット、または請求項6に記載のベクターを含み、請求項1〜3のいずれか一項に記載に記載のペプチドを発現しうるか、または発現しているトランスジェニック植物。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP20130306344 EP2853538A1 (en) | 2013-09-27 | 2013-09-27 | Analogues of temporin-SHa and uses thereof |
EP13306344.6 | 2013-09-27 | ||
PCT/EP2014/070633 WO2015044356A1 (en) | 2013-09-27 | 2014-09-26 | ANALOGUES OF TEMPORIN-SHa AND USES THEREOF |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2016539658A true JP2016539658A (ja) | 2016-12-22 |
JP6669656B2 JP6669656B2 (ja) | 2020-03-18 |
Family
ID=49448070
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2016544764A Expired - Fee Related JP6669656B2 (ja) | 2013-09-27 | 2014-09-26 | テンポリンSHaのアナログおよびその使用 |
Country Status (7)
Country | Link |
---|---|
US (1) | US9932376B2 (ja) |
EP (2) | EP2853538A1 (ja) |
JP (1) | JP6669656B2 (ja) |
BR (1) | BR112016006424A2 (ja) |
CA (1) | CA2924035A1 (ja) |
ES (1) | ES2691323T3 (ja) |
WO (1) | WO2015044356A1 (ja) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2022259007A1 (en) | 2021-06-11 | 2022-12-15 | Sorbonne Universite | Short antimicrobial peptides |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2012520665A (ja) * | 2009-03-19 | 2012-09-10 | ユニヴエルシテ・ピエール・エ・マリー・キユリー・パリ・シス | テンポリン−SHa類縁体及びその使用 |
Family Cites Families (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IL71691A (en) | 1984-04-27 | 1991-04-15 | Yeda Res & Dev | Production of interferon-ypsilon |
US5047335A (en) | 1988-12-21 | 1991-09-10 | The Regents Of The University Of Calif. | Process for controlling intracellular glycosylation of proteins |
AU1194092A (en) | 1991-02-06 | 1992-09-07 | Georgetown University | Receptor blocking peptides of fibroblast growth factor receptor |
US5916872A (en) | 1996-07-24 | 1999-06-29 | Intrabiotics Pharmaceuticals, Inc. | Cyclic peptides having broad spectrum antimicrobial activity |
JP2002538828A (ja) | 1999-03-17 | 2002-11-19 | ユニバーシティ オブ ビクトリア イノベーション アンド ディベロップメント コーポレーション | 広域性病原体に耐性を有するトランスジェニック植物 |
DE60115613T2 (de) | 2000-03-22 | 2006-08-24 | Octagene Gmbh | Herstellung von rekombinanten muteine des blutgerinnungsfaktors viii in humanen zellinien |
WO2005006938A2 (en) | 2003-07-18 | 2005-01-27 | Technion Research & Development Foundation Ltd. | Anti-microbial medical implants and uses thereof |
US7667089B2 (en) | 2004-04-09 | 2010-02-23 | National Chung Hsing University | Transgenic mammal secreting B-domain deleted human FVII in its milk |
WO2005123928A1 (en) | 2004-06-08 | 2005-12-29 | Battelle Memorial Institute | Production of human coagulation factor viii from plant cells and whole plants |
-
2013
- 2013-09-27 EP EP20130306344 patent/EP2853538A1/en not_active Withdrawn
-
2014
- 2014-09-26 US US15/021,948 patent/US9932376B2/en active Active
- 2014-09-26 JP JP2016544764A patent/JP6669656B2/ja not_active Expired - Fee Related
- 2014-09-26 CA CA2924035A patent/CA2924035A1/en not_active Abandoned
- 2014-09-26 EP EP14781114.5A patent/EP3049432B1/en not_active Not-in-force
- 2014-09-26 ES ES14781114.5T patent/ES2691323T3/es active Active
- 2014-09-26 WO PCT/EP2014/070633 patent/WO2015044356A1/en active Application Filing
- 2014-09-26 BR BR112016006424A patent/BR112016006424A2/pt not_active Application Discontinuation
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2012520665A (ja) * | 2009-03-19 | 2012-09-10 | ユニヴエルシテ・ピエール・エ・マリー・キユリー・パリ・シス | テンポリン−SHa類縁体及びその使用 |
Non-Patent Citations (2)
Title |
---|
CHEM BIOL DRUG DES, 2012, VOL. 79, PP. 653-662, JPN6018023029 * |
METHODS, 2007, VOL. 42, PP. 349-357, JPN6018023030 * |
Also Published As
Publication number | Publication date |
---|---|
EP3049432A1 (en) | 2016-08-03 |
EP3049432B1 (en) | 2018-08-15 |
US20160280749A1 (en) | 2016-09-29 |
ES2691323T3 (es) | 2018-11-26 |
WO2015044356A1 (en) | 2015-04-02 |
BR112016006424A2 (pt) | 2017-09-26 |
EP2853538A1 (en) | 2015-04-01 |
CA2924035A1 (en) | 2015-04-02 |
JP6669656B2 (ja) | 2020-03-18 |
US9932376B2 (en) | 2018-04-03 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Sarkar et al. | Antimicrobial peptides and proteins: From nature’s reservoir to the laboratory and beyond | |
Kosikowska et al. | Antimicrobial peptides (AMPs) as drug candidates: a patent review (2003–2015) | |
ES2784484T3 (es) | Péptido antimicrobiano | |
EP3274472B1 (en) | Antimicrobial peptides and methods of use thereof | |
WO2016161997A1 (en) | Antimicrobial peptides and their use for the treatment of topical infections | |
DK3087092T3 (en) | ANTIMICROBIAL PEPTID AND APPLICATIONS THEREOF | |
US9522942B2 (en) | Analogs of temporin-SHa and uses thereof | |
CN101775068A (zh) | 新的天然抗菌肽、其编码序列及用途 | |
JP6669656B2 (ja) | テンポリンSHaのアナログおよびその使用 | |
CN115043924B (zh) | 一种改造体抗菌肽及其应用 | |
WO2022259007A1 (en) | Short antimicrobial peptides | |
US20030208035A1 (en) | Antifungal and/or antibacterial peptides, preparation methods, compositions containing same and methods of treating mammals and/or plants | |
KR102146937B1 (ko) | 왕사마귀로부터 유래된 테노데라신-1 펩타이드, 이를 유효성분으로 포함하는 항균, 항진균 또는 항염증용 조성물 | |
KR101931572B1 (ko) | 융합 항균펩타이드 파제인 또는 이를 합성하는 방법 | |
EP3838286A1 (en) | Antimicrobial peptide from polistes gallicus venom and its analogs | |
KR20170054587A (ko) | 융합 항균펩타이드 p9p12 및 이를 합성하는 방법 | |
AU2015396744B2 (en) | A method of in vivo treatment | |
Barboza-Corona et al. | Antimicrobial Peptides: Current and Potential Applications in Biomedical Therapies |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20170802 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20180614 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20180626 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20180925 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20190326 |
|
A711 | Notification of change in applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A712 Effective date: 20190529 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20190603 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20190529 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20190925 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20200204 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20200227 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6669656 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
LAPS | Cancellation because of no payment of annual fees |